Glycosylated Haemoglobin

These laboratory tests are used to assess control in diabetes.

Chromatography of normal adult blood divides into two parts:

• Hb A (HbA0) 92-94%
• Hb A1 (6-8%) where the B chain has an additional glucose group.

HbA1 itself consists of three different glycosylations, the HbA1c subgroup being the most useful, usually measured by isoelectric focusing or electrophoresis.
The glycation of haemoglobin occurs at a variable (non-linear rate) over time, during the whole lifespan of the red blood cell (normally 120 days). This means the relative proportion of glycosylated haemoglobin at any one time depends on the mean glucose level over the last 120 days.
Normal levels (laboratory normal "range") will differ depending on whether HbA1 or HbA1c is measured, and the method used - use your lab's reference range (EDTA (FBC) bottle).¹
Glycated haemoglobin (HbA1c) is usually a reliable indicator of diabetic control except in the following situations:

• Where the average RBC lifespan is significantly less than120 days - such will usually give rise to low HbA1c results as 50% of glycosylation occurs in days 90-120.²
  Common Causes:¹
  • Increased red cell turnover: blood loss, haemolysis, haemoglobinopathies and red cell disorders, myelodysplastic disease
  • Interference with test (depends on method used: Persistent fetal haemoglobin and haemoglobin variants, carbamylated haemoglobin (uraemic patients)
• In patients who fluctuate between very high and very low levels - glycosylated haemoglobin readings can be misleading (clinician should compare with extra information obtained from home capillary blood glucose tests).
• HbA1c can be very useful in identifying patients who may be presenting an unrealistically good report of their home glucose tests.

Other important points to consider:

• The general diabetes control and complications trial (DCCT) suggested an HbA1c target of < 7.5% (ideally < 6.5% to 7.0%) for the management of diabetic patients, which should be individualised and agreed with the patient (considering co-morbidity, life expectancy, hypoglycaemia frequency, etc.).³
• Do not test more frequently than every 3 months - and avoid overinterpreting results. Look for trends rather than the difference in two consecutive results - test imprecision varies with method used and is typically 3-4%.
• HbA1c is not a diagnostic test for diabetes, nor should it be used to screen for diabetes.
• Mean plasma glucose results are 10-15% higher than the equivalent HbA1c; ie an HbA1c of 7% correlates to an average plasma glucose of 9.5 mmol/l.⁴ Also remember that most patient self test machines are calibrated for whole blood glucose, which is around 13% lower than equivalent plasma glucose values and so more comparable with the HbA1c.⁵

Fructosamine is the glycalated fraction of all plasma proteins (predominantly albumin), but considered less accurate because of the numerous factors affecting the half-lives of the many components. It generally reflects average glucose in the previous two weeks.